Document Detail

Protein-disulfide isomerase regulates the thyroid hormone receptor-mediated gene expression via redox factor-1 through thiol reduction-oxidation.
MedLine Citation:
PMID:  23148211     Owner:  NLM     Status:  MEDLINE    
Protein-disulfide isomerase (PDI) is a dithiol/disulfide oxidoreductase that regulates the redox state of proteins. We previously found that overexpression of PDI in rat pituitary tumor (GH3) cells suppresses 3,3',5-triiodothyronine (T(3))-stimulated growth hormone (GH) expression, suggesting the contribution of PDI to the T(3)-mediated gene expression via thyroid hormone receptor (TR). In the present study, we have clarified the mechanism of regulation by which TR function is regulated by PDI. Overexpression of wild-type but not redox-inactive mutant PDI suppressed the T(3)-induced GH expression, suggesting that the redox activity of PDI contributes to the suppression of GH. We considered that PDI regulates the redox state of the TR and focused on redox factor-1 (Ref-1) as a mediator of the redox regulation of TR by PDI. Interaction between Ref-1 and TRβ1 was detected. Overexpression of wild-type but not C64S Ref-1 facilitated the GH expression, suggesting that redox activity of Cys-64 in Ref-1 is involved in the TR-mediated gene expression. Moreover, PDI interacted with Ref-1 and changed the redox state of Ref-1, suggesting that PDI controls the redox state of Ref-1. Our studies suggested that Ref-1 contributes to TR-mediated gene expression and that the redox state of Ref-1 is regulated by PDI. Redox regulation of PDI via Ref-1 is a new aspect of PDI function.
Shoko Hashimoto; Susumu Imaoka
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  288     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-03-26     Revised Date:  2014-01-23    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1706-16     Citation Subset:  IM    
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MeSH Terms
Cell Line, Tumor
DNA-(Apurinic or Apyrimidinic Site) Lyase / genetics*,  metabolism
Gene Expression Regulation / drug effects*
Genes, Reporter
Growth Hormone / genetics,  metabolism
Isoenzymes / genetics,  metabolism
Protein Disulfide-Isomerases / genetics*,  metabolism
Signal Transduction / drug effects
Thyroid Hormone Receptors beta / genetics*,  metabolism
Triiodothyronine / pharmacology
Reg. No./Substance:
0/Isoenzymes; 0/Thyroid Hormone Receptors beta; 06LU7C9H1V/Triiodothyronine; 9002-72-6/Growth Hormone; EC 1.13.12.-/Luciferases; EC protein, rat; EC or Apyrimidinic Site) Lyase; EC Disulfide-Isomerases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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